KEGG   PATHWAY: mmu04722
Entry
mmu04722                    Pathway                                
Name
Neurotrophin signaling pathway - Mus musculus (house mouse)
Description
Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory.
Class
Organismal Systems; Nervous system
Pathway map
mmu04722  Neurotrophin signaling pathway
mmu04722

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
18049  Ngf; nerve growth factor [KO:K02582]
12064  Bdnf; brain derived neurotrophic factor [KO:K04355]
78405  Ntf5; neurotrophin 5 [KO:K12457]
18205  Ntf3; neurotrophin 3 [KO:K04356]
18211  Ntrk1; neurotrophic tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
18212  Ntrk2; neurotrophic tyrosine kinase, receptor, type 2 [KO:K04360] [EC:2.7.10.1]
18213  Ntrk3; neurotrophic tyrosine kinase, receptor, type 3 [KO:K05101] [EC:2.7.10.1]
23921  Sh2b2; SH2B adaptor protein 2 [KO:K07193]
20399  Sh2b1; SH2B adaptor protein 1 [KO:K12459]
16923  Sh2b3; SH2B adaptor protein 3 [KO:K12459]
14784  Grb2; growth factor receptor bound protein 2 [KO:K04364]
20662  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
20663  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
109880  Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110651  Rps6ka3; ribosomal protein S6 kinase polypeptide 3 [KO:K04373] [EC:2.7.11.1]
20111  Rps6ka1; ribosomal protein S6 kinase polypeptide 1 [KO:K04373] [EC:2.7.11.1]
20112  Rps6ka2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04373] [EC:2.7.11.1]
67071  Rps6ka6; ribosomal protein S6 kinase polypeptide 6 [KO:K04373] [EC:2.7.11.1]
73086  Rps6ka5; ribosomal protein S6 kinase, polypeptide 5 [KO:K04445] [EC:2.7.11.1]
11911  Atf4; activating transcription factor 4 [KO:K04374]
12043  Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]
77480  Kidins220; kinase D-interacting substrate 220 [KO:K12460]
327826  Frs2; fibroblast growth factor receptor substrate 2 [KO:K12461]
12928  Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438]
12929  Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438]
107746  Rapgef1; Rap guanine nucleotide exchange factor (GEF) 1 [KO:K06277]
109905  Rap1a; RAS-related protein 1a [KO:K04353]
215449  Rap1b; RAS related protein 1b [KO:K07836]
26406  Map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
23938  Map2k5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
23939  Mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
17164  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
20416  Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279]
216148  Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
20418  Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448]
271849  Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
14388  Gab1; growth factor receptor bound protein 2-associated protein 1 [KO:K09593]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
18036  Nfkbib; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, beta [KO:K02581]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18037  Nfkbie; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, epsilon [KO:K05872]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
56484  Foxo3; forkhead box O3 [KO:K09408]
14103  Fasl; Fas ligand [KO:K04389]
12015  Bad; BCL2-associated agonist of cell death [KO:K02158]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
18607  Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
16367  Irs1; insulin receptor substrate 1 [KO:K16172]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
18753  Prkcd; protein kinase C, delta [KO:K06068] [EC:2.7.11.13]
12313  Calm1; calmodulin 1 [KO:K02183]
80796  Calm4; calmodulin 4 [KO:K02183]
12315  Calm3; calmodulin 3 [KO:K02183]
12314  Calm2; calmodulin 2 [KO:K02183]
70405  Calml3; calmodulin-like 3 [KO:K02183]
494124  Calm5; calmodulin 5 [KO:K02183]
75600  Calml4; calmodulin-like 4 [KO:K02183]
108058  Camk2d; calcium/calmodulin-dependent protein kinase II, delta [KO:K04515] [EC:2.7.11.17]
12325  Camk2g; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
12323  Camk2b; calcium/calmodulin-dependent protein kinase II, beta [KO:K04515] [EC:2.7.11.17]
12322  Camk2a; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
12326  Camk4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
11350  Abl1; c-abl oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
19247  Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
17179  Matk; megakaryocyte-associated tyrosine kinase [KO:K08888] [EC:2.7.10.2]
18053  Ngfr; nerve growth factor receptor (TNFR superfamily, member 16) [KO:K02583]
11857  Arhgdib; Rho, GDP dissociation inhibitor beta [KO:K12462]
192662  Arhgdia; Rho GDP dissociation inhibitor alpha [KO:K12462]
14570  Arhgdig; Rho GDP dissociation inhibitor gamma [KO:K12462]
11848  Rhoa; ras homolog family member A [KO:K04513]
67653  4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513]
12540  Cdc42; cell division cycle 42 [KO:K04393]
19353  Rac1; Rac family small GTPase 1 [KO:K04392]
26401  Map3k1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
26408  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
26400  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
16476  Jun; jun proto-oncogene [KO:K04448]
22059  Trp53; transformation related protein 53 [KO:K04451]
12028  Bax; BCL2-associated X protein [KO:K02159]
22062  Trp73; transformation related protein 73 [KO:K10148]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
65020  Zfp110; zinc finger protein 110 [KO:K12458]
170936  Zfp369; zinc finger protein 369 [KO:K12458]
72843  Prdm4; PR domain containing 4 [KO:K12463] [EC:2.1.1.-]
94275  Maged1; MAGE family member D1 [KO:K12464]
12070  Bex3; brain expressed X-linked 3 [KO:K12465]
22627  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [KO:K06630]
192656  Ripk2; receptor (TNFRSF)-interacting serine-threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
16179  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
108960  Irak2; interleukin-1 receptor-associated kinase 2 [KO:K04731] [EC:2.7.11.1]
73914  Irak3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
266632  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
20661  Sort1; sortilin 1 [KO:K12388]
19164  Psen1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
19165  Psen2; presenilin 2 [KO:K04522] [EC:3.4.23.-]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00195  N-Acylsphingosine
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:12676795
  Authors
Huang EJ, Reichardt LF.
  Title
Trk receptors: roles in neuronal signal transduction.
  Journal
Annu Rev Biochem 72:609-42 (2003)
DOI:10.1146/annurev.biochem.72.121801.161629
Reference
PMID:11399424
  Authors
Patapoutian A, Reichardt LF
  Title
Trk receptors: mediators of neurotrophin action.
  Journal
Curr Opin Neurobiol 11:272-80 (2001)
DOI:10.1016/S0959-4388(00)00208-7
Reference
PMID:16699811
  Authors
Arevalo JC, Wu SH
  Title
Neurotrophin signaling: many exciting surprises!
  Journal
Cell Mol Life Sci 63:1523-37 (2006)
DOI:10.1007/s00018-006-6010-1
Reference
PMID:14704852
  Authors
Teng KK, Hempstead BL
  Title
Neurotrophins and their receptors: signaling trios in complex biological systems.
  Journal
Cell Mol Life Sci 61:35-48 (2004)
DOI:10.1007/s00018-003-3099-3
Reference
PMID:11529497
  Authors
Miller FD, Kaplan DR
  Title
Neurotrophin signalling pathways regulating neuronal apoptosis.
  Journal
Cell Mol Life Sci 58:1045-53 (2001)
DOI:10.1007/PL00000919
Reference
PMID:10851172
  Authors
Kaplan DR, Miller FD
  Title
Neurotrophin signal transduction in the nervous system.
  Journal
Curr Opin Neurobiol 10:381-91 (2000)
DOI:10.1016/S0959-4388(00)00092-1
Reference
PMID:16939974
  Authors
Reichardt LF
  Title
Neurotrophin-regulated signalling pathways.
  Journal
Philos Trans R Soc Lond B Biol Sci 361:1545-64 (2006)
DOI:10.1098/rstb.2006.1894
Reference
PMID:16856873
  Authors
Zampieri N, Chao MV
  Title
Mechanisms of neurotrophin receptor signalling.
  Journal
Biochem Soc Trans 34:607-11 (2006)
DOI:10.1042/BST0340607
Reference
PMID:15499580
  Authors
Rose CR, Blum R, Kafitz KW, Kovalchuk Y, Konnerth A
  Title
From modulator to mediator: rapid effects of BDNF on ion channels.
  Journal
Bioessays 26:1185-94 (2004)
DOI:10.1002/bies.20118
Reference
PMID:10812966
  Authors
Yano H, Chao MV
  Title
Neurotrophin receptor structure and interactions.
  Journal
Pharm Acta Helv 74:253-60 (2000)
DOI:10.1016/s0031-6865(99)00036-9
Reference
PMID:10764727
  Authors
Mukai J, Hachiya T, Shoji-Hoshino S, Kimura MT, Nadano D, Suvanto P, Hanaoka T, Li Y, Irie S, Greene LA, Sato TA
  Title
NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR.
  Journal
J Biol Chem 275:17566-70 (2000)
DOI:10.1074/jbc.C000140200
Reference
PMID:10985348
  Authors
Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA
  Title
NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis.
  Journal
Neuron 27:279-88 (2000)
DOI:10.1016/S0896-6273(00)00036-2
Related
pathway
mmu04010  MAPK signaling pathway
mmu04120  Ubiquitin mediated proteolysis
mmu04210  Apoptosis
mmu04720  Long-term potentiation
mmu04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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